Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
J Med Genet. 2013 Sep;50(9):579-84. doi: 10.1136/jmedgenet-2013-101659. Epub 2013 May 24.
Metacarpal 4-5 fusion (MF4; MIM %309630) is a rare congenital malformation of the hand characterised by the partial or complete fusion of the fourth and fifth metacarpals. The anomaly occurs as an isolated trait or part of a genetic syndrome.
To search for disease-causing mutation, whole exome sequencing (WES) was performed on samples from a single trio. Before WES, molecular screening including gene sequencing and array comparative genomic hybridisation was applied. Validation of WES and segregation studies were done using routine Sanger sequencing.
Exome sequencing detected a nonsense mutation (c.C535T; p.R179X) in exon 3 of the FGF16 gene, which maps to chromosome Xq21.1. Mutational screening of the FGF16 gene performed in an unrelated proband of different ethnicity showed another nonsense mutation in exon 3 (c.C470A; p.S157X).
This study shows that truncating mutations of FGF16 are associated with X-linked recessive metacarpal 4-5 fusion. The study provides evidence for the involvement of FGF16 in the fine tuning of the human skeleton of the hand.
掌骨 4-5 融合（MF4；MIM%309630）是一种罕见的手部先天性畸形，其特征为第四和第五掌骨部分或完全融合。该异常作为一种孤立的特征或遗传综合征的一部分出现。
为了寻找致病突变，对一个单体三的样本进行了全外显子组测序（WES）。在进行 WES 之前，应用了包括基因测序和阵列比较基因组杂交的分子筛选。使用常规 Sanger 测序进行了 WES 的验证和分离研究。
外显子组测序在 Xq21.1 染色体上的 FGF16 基因的第 3 外显子中检测到一个无义突变（c.C535T；p.R179X）。对不同种族的另一个无关先证者进行的 FGF16 基因突变筛查显示，第 3 外显子中存在另一个无义突变（c.C470A；p.S157X）。
这项研究表明，FGF16 的截断突变与 X 连锁隐性掌骨 4-5 融合有关。该研究为 FGF16 参与人类手部骨骼的精细调节提供了证据。
